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Delirium is a frequent neurocognitive complication in cancer patients, particularly in advanced stage and terminal disease. It is associated with increased morbidity and mortality and is a critical source of stress for patients and caregivers. For healthcare staff, delirium poses significant challenges in diagnosis and treatment as well as assessment of other symptoms due to its fluctuating nature, communication impediments, and possible agitation in hyperactive subtypes. Pathophysiological mechanisms underlying delirium are complex, but the approach to adequate symptom management consists of nonpharmacological strategies as well as the use of antipsychotic agents. However, when nonreversible and refractory delirium occurs, palliative sedation is an invaluable treatment option and may be offered after careful consideration. This short review attempts to cover important aspects of clinical features of delirium, diagnostic and treatment strategies as well as the role of palliative sedation in refractory situations in delirious cancer patients at the end of life.